Research and Development for a Gadolinium Doped Water Cherenkov Detector

The proposed introduction of a soluble gadolinium (Gd) compound into water Cherenkov detectors can result in a high efficiency for the detection of free neutrons capturing on the Gd. The delayed 8 MeV gamma cascades produced by these captures, in coincidence with a prompt positron signal, serve to uniquely identify electron antineutrinos interacting via inverse beta decay. Such coincidence detection can reduce backgrounds, allowing a large Gd-enhanced water Cherenkov detector to make the first observation of supernova relic neutrinos and high precision measurements of Japan's reactor antineutrino flux, while still allowing for all current physics studies to be continued. Now, a dedicated Gd test facility is operating in the Kamioka Mine. This new facility houses everything needed to successfully operate a Gd doped water Cherenkov detector. Successful running of this facility will demonstrate that adding Gd salt to SK is both safe for the detector and is capable of delivering the expected physics benefits.Comment: Proceedings from the Technology and Instrumentation for Particle Physics 2011 (TIPP 2011) conferenc

Solar Neutrino Results from Super-Kamiokande

Super-Kamiokande-IV (SK-IV) data taking began in September of 2008, after upgrading the electronics and data acquisition system. Due to these upgrades and improvements to water system dynamics, calibration and analysis techniques, a solar neutrino signal could be extracted at recoil electron kinetic energies as low as 3.5 MeV. When the SK-IV data is combined with the previous three SK phases, the SK extracted solar neutrino flux is found to be [2.37\pm0.015\mbox{(stat.)}\pm0.04\mbox{(syst.)}]\times10^6/(cm$^{2}$sec). The combination of the SK recoil electron energy spectra slightly favors distortions due to a changing electron flavor content. Such distortions are predicted when assuming standard solar neutrino oscillation solutions. An extended maximum likelihood fit to the amplitude of the expected solar zenith angle variation of the neutrino-electron elastic scattering rate results in a day-night asymmetry of $[-3.2\pm1.1$(stat.)$\pm0.5$(syst.)]$\%$. A solar neutrino global oscillation analysis including all current solar neutrino data, as well as KamLAND reactor antineutrino data, measures the solar mixing angle as $\sin^2\theta_{12}=0.305\pm0.013$, the solar neutrino mass squared splitting as $\Delta m^2_{21}=7.49^{+0.19}_{-0.17}\times10^{-5}$eV$^2$ and $\sin^2\theta_{13}=0.026^{+0.017}_{-0.012}$

Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial

PURPOSE Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist. METHODS Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m2 once every 3 weeks for three cycles before RT and 20 mg/m2 once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (\u3c 4, \u3e 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors. RESULTS After a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA \u3c 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA \u3c 4 ng/mL. CONCLUSION Adding docetaxel to ADT + RT did not prolong OS in men with unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA \u3c 4 ng/mL by reducing PC-specific mortality

Immunity to HIV in Early Life

The developing immune system is adapted to the exposure to a plethora of pathogenic and non-pathogenic antigens encountered in utero and after birth, requiring a fine balance between protective immunity and immune tolerance. In early stages of life, this tolerogenic state of the innate and adaptive immune system and the lack of immunological memory render the host more susceptible to infectious pathogens like HIV. HIV pathogenesis is different in children, compared to adults, with more rapid disease progression and a substantial lack of control of viremia compared to adults. Plasma viral load remains high during infancy and only declines gradually over several years in line with immune maturation, even in rare cases where children maintain normal CD4 T-lymphocyte counts for several years without antiretroviral therapy (ART). These pediatric slow progressors also typically show low levels of immune activation despite persistently high viremia, resembling the phenotype of natural hosts of SIV infection. The lack of immunological memory places the fetus and the newborn at higher risk of infections; however, it may also provide an opportunity for unique interventions. Frequencies of central memory CD4+ T-lymphocytes, one of the main cellular reservoirs of HIV, are very low in the newborn child, so immediate ART could prevent the establishment of persistent viral reservoirs and result in “functional cure.” However, as recently demonstrated in the case report of the “Mississippi child” who experienced viral rebound after more than 2 years off ART, additional immunomodulatory strategies might be required for sustained viral suppression after ART cessation. In this review, we discuss the interactions between HIV and the developing immune system in children and the potential implications for therapeutic and prophylactic interventions

Direct integration of intensity-level data from Affymetrix and Illumina microarrays improves statistical power for robust reanalysis

BACKGROUND: Affymetrix GeneChips and Illumina BeadArrays are the most widely used commercial single channel gene expression microarrays. Public data repositories are an extremely valuable resource, providing array-derived gene expression measurements from many thousands of experiments. Unfortunately many of these studies are underpowered and it is desirable to improve power by combining data from more than one study; we sought to determine whether platform-specific bias precludes direct integration of probe intensity signals for combined reanalysis. RESULTS: Using Affymetrix and Illumina data from the microarray quality control project, from our own clinical samples, and from additional publicly available datasets we evaluated several approaches to directly integrate intensity level expression data from the two platforms. After mapping probe sequences to Ensembl genes we demonstrate that, ComBat and cross platform normalisation (XPN), significantly outperform mean-centering and distance-weighted discrimination (DWD) in terms of minimising inter-platform variance. In particular we observed that DWD, a popular method used in a number of previous studies, removed systematic bias at the expense of genuine biological variability, potentially reducing legitimate biological differences from integrated datasets. CONCLUSION: Normalised and batch-corrected intensity-level data from Affymetrix and Illumina microarrays can be directly combined to generate biologically meaningful results with improved statistical power for robust, integrated reanalysis

Reporting Gleason grade/score in synoptic reports of radical prostatectomies

Context: The format of a synoptic report can significantly affect the accuracy, speed, and preference with which a reader can retrieve information. Objective: The objective of this study is to compare different formats of Gleason grading/score in synoptic reports of radical prostatectomies. Methods: The performance of 16 nonpathologists (cancer registrars, MDs, medical non-MDs, and nonmedical) at identifying specific information in various formatted synoptic reports using a computerized quiz that measured both accuracy and speed. Results: Compared to the standard format (primary, secondary, tertiary grades, and total score on separate lines), omitting tertiary grade when "Not applicable" reduced accuracy (72 vs. 97%, P total score) were associated with increased speed of data extraction (18 and 24%, respectively, P < 0.001). The single line format was more accurate (100% vs. 97%, P = 0.02). No user preferred the biopsy format, and only 7/16 users preferred the single line format. Conclusions : Different report formats for Gleason grading significantly affect users speed, accuracy, and preference; users do not always prefer either speed or accuracy

Novel methods for groundwater monitoring within regions of oil and gas production

As California enters its fourth year of drought, protecting shallow groundwater quality for municipal, domestic and agricultural use becomes critically important. Many of California’s sedimentary basins host both potable groundwater aquifers and hydrocarbon-producing zones, and Senate Bill 4 (Pavely, 2013) requires groundwater monitoring within hydrocarbon zones that potentially impact shallow aquifers by certain types of oil production. One approach to understanding the relationship between deeply seated fluids associated with oil production and shallow drinking water aquifers is to establish current ambient groundwater quality conditions using available data (both current and historic), then develop a predictive mixing model between ambient groundwater and “produced” waters associated with oil production. In addition, in order to fill datagaps useful for the model, novel methods of analyzing certain chemical analytes in produced waters must be developed. Produced waters typically contain complex hydrogeochemical matrices (e.g., high salinity, TDS, etc.) but also contain effective isotopic tracers such as isotopes of radium. Utilizing produced water samples from three large oil fields in California, a novel method to analyze radium-226 in produced waters was developed. The analytical method utilizes liquid scintillation counting (LSC) to provide accurate and efficient results with a two-week turn around time. Radium analysis in produced water samples will further refine the mixing model and therefore groundwater monitoring programs in oil producing regions. Data from the Kern County groundwater basin demonstrates the novel groundwater monitoring methods. The San Joaquin Valley’s Kern County groundwater basin contains the majority of California’s oil production (~80% of the active wells in California). In addition, the county relies almost entirely on groundwater for its water supply, and is the most productive agricultural county in the US. Considering Kern County’s historically stressed groundwater system, the Department of Water Resources ranks the basin as a high priority in the statewide groundwater elevation monitoring (CASGEM) program. This research consists of a database investigation to define the current water quality conditions within Kern County’s groundwater system and to examine the relationship between shallow groundwater and produced waters. An end-member mixing model utilizing multivariate statistics compares the geochemical data between the two distinct waters. Two publically available data sets are used to define the end-members: the California State Water Resources Control Board’s Groundwater Ambient Monitoring and Assessment program data are used to define the shallow zone, and the USGS Produced Waters data are used to define the deep formation waters. The multivariate mixing model indicates that six common groundwater chemical analytes (Ca, Cl, Mg, Na, SO4 and TDS) distinctly segregate shallow groundwater from produced waters. The multivariate model will aid groundwater monitoring programs by providing a statistical test of whether deeply seated basin fluids are mixing with shallow groundwater